Forty years after the Haddonfield murders in 1978, two journalists, Aaron Korey and Dana Haines, travel to Smith's Grove Sanitarium to interview Michael Myers, who was captured after Dr. Samuel Loomis shot him off of the Doyle house balcony at the end of the movie. Dr. Ranbir Sartain, Michael's new psychiatrist after Dr. Loomis' death, inform them that Michael is able to speak, but chooses not to. Dana records the event as Aaron approaches Michael and talks to him, but fails to get him to speak, even after showing him his mask and mentioning Laurie Strode.
The two journalists leave Smith's Grove Sanitarium and drive to Laurie's house, a heavily fortified and decrepit homestead, and bribe her for an interview, which she reluctantly accepts. Laurie has spent the last forty years dealing with post-traumatic stress and preparing for Michael's inevitable return. Her feelings have resulted in two failed marriages and losing custody of her daughter Karen at a young age. Aaron and Dana tell Laurie their interest in finding out why Michael committed the murders in 1978 and ask her to meet with him in a final attempt to get him to speak before he's transferred to a maximum security prison. Laurie kicks them out of her house, but not before taking the money they offered.
As the transport is being prepared and patients are loaded onto the bus, Dr. Sartain insists on accompanying Michael, and the bus departs. In Haddonfield, Laurie's granddaughter and Karen's daughter, Allyson, is walking to school with two friends and tells them the stress that her family endures due to her grandmother's past, and debunks the town rumor that Michael is Laurie's brother. In class, Allyson looks out of the window to see Laurie watching her. She meets with her grandmother who gives her the three thousand dollars from Aaron and Dana and tells her to have fun. During a family dinner at Karen's house, Laurie arrives and has a panic attack and Allyson comforts her. Meanwhile, the bus transport crashed in a ditch, the security guards were killed, and the inmates were scattered about the road. A man and his son driving down the road happen upon the bus and investigate. While the father disappears, his son grabs a rifle from the truck and encounters a fatally wounded security guard that tells him to run. He investigates the bus and is startled by Dr. Sartain, shooting him in the shoulder accidentally. Fleeing back to the truck, he calls the police; Michael appears from the back seat and kills him.
The following morning, Sheriff Frank Hawkins explains to a deputy that Michael Myers escaped the transport and will most certainly return to Haddonfield to finish what he started four decades prior. Aaron and Dana arrive at a gas station; Dana leaves Aaron to use the bathroom while he goes inside to pay for the gas. With the inside of the station deserted, he stumbles upon a dead mechanic missing his overalls and a cashier whose jaw was ripped open. Meanwhile, Michael attacks Dana in the bathroom, and when Aaron arrives to save Dana, Michael kills him by bashing him into the door numerous times, killing him, before strangling Dana to death. Michael inspects their vehicle and recovers his mask, putting it on. Laurie learns about the transport crash and breaks into Karen's house to demonstrate her lack of security. After a brief argument about Michael with Karen and her husband, Ray, Laurie leaves and heads to the gas station in time to witness the bodies of Aaron and Dana being recovered.
On Halloween night, Michael wanders a populated street in Haddonfield, littered with families and children trick-or-treating. He finds his way into a shed behind a house and takes a hammer before going inside to kill the sole occupant. He replaces the hammer with a kitchen knife and moves to the house next door, killing another woman by stabbing the knife through her throat. Allyson is at a school-sanctioned Halloween party with her friends and receives a call from Vicky, inviting her to come over once Julian, the kid she's babysitting, falls asleep. Allyson gets into an altercation with her boyfriend, Cameron, who throws her phone, just as Laurie was calling to warn her to go home. At Julian's house, he tells Vicky that he saw a masked man standing in the doorway, but Vicky dismisses it as his imagination and puts Julian to bed as her boyfriend, Dave, arrives. As Vicky checks the closet at Julian's request, she opens the door and is attacked by Michael who was hiding inside; Julian flees the house and calls the police. Laurie, patrolling the streets in her truck, hears the dispatch call on her CB radio and hurries to the house, where Sheriff Hawkins is investigating. He finds Vicky's corpse and Laurie shoots Michael through a window, only to find out it's his reflection in a mirror. Laurie and Hawkins patrol behind the neighboring houses and find Michael; Laurie shoots him, but as she turns the corner, Michael is gone.
Allyson ditches her boyfriend at the party and allows her friend Oscar to walk her home. Allyson rejects his advances and Oscar lags behind, spotting Michael watching him. Oscar tries to escape, but is caught on a fence and Michael impales him. Allyson turns back and finds Oscar's body and is chased by Michael before finding refuge in a neighboring home. Karen and Ray arrive at Laurie's fortified home and wait for Allyson to arrive. Hawkins encounters Dr. Sartain and in turn, find Allyson during their search for Michael. Finding Michael, Hawkins runs him over with the police SUV and gets out of the vehicle to shoot Michael at point-blank range, despite Dr. Sartain's protests. Dr. Sartain stabs Hawkins in the throat with a blade hidden inside of a pen and kills him before taking Michael's mask and trying it on. Dr. Sartain loads Michael into the back of the vehicle with Allyson and drives to Laurie's house, intent on reuniting them. Michael regains consciousness and reclaims his mask, and Allyson informs Dr. Sartain that Michael spoke to her; distracted by demanding to know what Michael said, Michael breaks through the security barrier, forces Dr. Sartain out of the vehicle, and stomps on his head as Allyson flees on foot.
Ray steps outside to offer coffee to the police officers stationed outside Laurie's house and finds them dead. Michael appears behind Ray and strangles him. Laurie alerts Karen to Michael's arrival and sends her into the hidden safe room as she locks and barricades the front door. Michael breaks through the glass panels in the door and attacks Laurie, who escapes by shooting Michael's hand with a shotgun, stripping him of two fingers, forcing him to retreat. Laurie patrols her house room by room and seals each room off with security gates. Laurie encounters Michael upstairs; Allyson arrives as Laurie and Michael stab each other and witnesses Laurie fall from the balcony. When she investigates, Laurie is gone and Allyson makes her way into the safe room with Karen, who alerts Michael. As he appears, Karen shoots him with a rifle and stuns him. Laurie appears from the shadows and attacks Michael, sending him tumbling down the steps into the safe room.
Karen and Allyson leave the safe room, but Michael regains consciousness and grabs Karen's ankle. Allyson stabs Michael with his own knife and the two escape the room. Laurie flips a switch and metal bars spring into place, barricading the exit and trapping Michael in the safe room as it fills with gas. Laurie lights a flare and tosses it through the bars, setting the room ablaze with Michael in it. Laurie, Karen, and Allyson escape as the house is engulfed in flames and hitch a ride in the back of a pickup truck coming down the road. The three women embrace as they're taken to safety.